MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker

Abstract

<jats:p>Recent advances in ruminants’ milk-derived exosomes (EXO) have indicated a role of microRNAs (miRNAs) in cell-to-cell communication in dairy ruminants. The miRNAs EXO retain peculiar mechanisms of uptake from recipient cells, which enables the selective delivery of cargos, with a specific regulation of target genes. Although many studies have been published on the miRNAs contained in milk, less information is available on the role of miRNAs EXO, which are considered stable over time and resistant to digestion and milk processing. Several miRNAs EXO have been implicated in the cellular signaling pathway, as in the regulation of immune response. Moreover, they exert epigenetic control, as extenuating the expression of DNA methyltransferase 1. However, the study of miRNAs EXO is still challenging due to the difficulty of isolating EXO. In fact, there are not agreed protocols, and different methods, often time-consuming, are used, making it difficult to routinely process a large number of samples. The regulation of cell functions in mammary glands by miRNAs EXO, and their applications as genomic markers in livestock, is presented.</jats:p>

Milk Exosomes: Perspective Agents for Anticancer Drug Delivery

“…General issues concerning the isolation and characterization of exosomes are described in the guidelines of the International Society for Extracellular Vesicles [ 28 , 29 ]. Because the volume of milk obtained from single humans or animals may vary from milliliters to liters, the general protocol [ 1 ] of exosome isolation from milk samples usually starts with a series of centrifugations [ 6 ]: first, several sequential centrifugations at low speed of 600–1000× g to defat the milk and precipitate the cells, then 10,000–16,000× g to precipitate milk proteins, followed by one or several ultracentrifugations at 100,000–200,000× g [ 30 ] to isolate the exosomes. Some protocols include the stage of ultracentrifugation in the sucrose density gradient [ 31 ].…”

“…Exosomes are natural extracellular nanovesicles that participate in intercellular communication by carrying biologically active substances like proteins, microRNA, mRNA, DNA, and other molecules [ 1 , 2 ]. The carried compounds can be transported both inside and on the surface of exosomes [ 3 ].…”

Circulating microRNAs in Breast Milk and Their Potential Impact on the Infant

“…The gastrointestinal tract is a tough environment because of factors such as pH, RNases, the gut microbiota, or the intercellular junctions between enterocytes. After passing from the digestive tract to the circulation, the circulating enzymes, the immune system, the vascular endothelium, and the membrane itself involve potential hazards for the integrity of the miRNA [ 14 , 17 ].…”

“…In addition to the endogenous miRNAs, the potential impact of the exogenous ones has become even more significant in recent years [ 13 , 14 ]. Emerging evidence points out that miRNAs contained in different dietary sources can play a key role in epigenetic regulation processes and intercellular communication [ 15 , 16 , 17 ].…”

“…Many similarities have been found between the miRNA profile of human breast milk and that of the milk of other mammalian species [ 17 ]. A study that compared milk from different mammals found that approximately 91–92% of the miRNA profile expressed in human breast milk was also expressed in bovine and goat milk.…”